Location: Children's Nutrition Research CenterTitle: In utero glucocorticoid (GLC) exposure and maternal undernutrition reduce fetal skeletal muscle mass by different mechanisms in rats Author
Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: 11/18/2009
Publication Date: 5/1/2010
Citation: Gokulakrishnan, G., Estrada, I.J., Sosa, H.A., Watson, K.L., Fiorotto, M.L. 2010. In utero glucocorticoid (GLC) exposure and maternal undernutrition reduce fetal skeletal muscle mass by different mechanisms in rats [abstract]. In: Proceedings of the 2010 Pediatric Academic Societies Annual Conference, May 1-4, 2010, Vancouver, British Columbia, Canada. Paper No. 1340.3. Interpretive Summary:
Technical Abstract: Both maternal undernutrition and exposure of the fetus to above normal levels of GLC impair skeletal muscle growth. The degree to which the effects of maternal undernutrition on fetal skeletal muscle growth are a direct result of nutrient deficit or secondary to the presence of above normal GLC levels induced by maternal undernutrition is uncertain. To test the hypothesis that the effects of maternal undernutriton which result in a reduction in fetal skeletal muscle growth are independent of the effects of GLC. The aims were 1) to quantify the degree of fetal exposure to GLC during gestation by measuring expression levels of tyrosine aminotransferase (TAT), a GLC-inducible gene, in the term fetal liver. 2) To determine the changes in fetal muscle protein synthesis following GLC exposure and maternal nutrient restriction. Three groups (n=7/group) of timed-pregnant Sprague-Dawley (SD) rats were studied: Control (CON): ad libitum food intake; no dexamethasone; Dexamethasone (DEX): ad libitum food intake; dexamethasone (1 mg/L drinking water ad lib from embryonic day (ED)13 to 21). Pair-fed (PF): pair-fed to DEX group from ED 13 to 21; no DEX. On ED 22 (term), prior to surgical delivery, dams were injected with [H]phenylalanine for in vivo measurements of fetal leg and diaphragm protein synthesis rates (FSR). After delivery, fetal muscles and liver were rapidly collected for measurement of protein content and [H]phenylalanine incorporation, and tyrosine aminotransferase (TAT) expression levels, respectively. DEX treatment reduced maternal food intake by 13% (P<0.001). Fetal liver TAT expression was elevated in the DEX group (P<0.01) with no difference between CON and PF. DEX and PF muscle protein masses were 60% and 80% of CON values, respectively (P<0.01). Muscle protein FSR decreased by 35% in DEX fetuses (P<0.001) with no difference between PF and CON values. In conclusion, the reduction in fetal muscle mass as a result of maternal undernutrition was not attributable to increased fetal exposure to GLC. GLC exacerbated the effect of reduced maternal food intake on muscle mass. The differences in FSR responses suggest that the negative effects of GLC and reduced maternal food intake on skeletal muscle growth are mediated by different mechanisms.